The present invention relates to a process for the enantioselective preparation of oligomers consisting of α-amino acid isomers and co-oligomers consisting of α-hydroxy carboxylic acid isomers and α-amino acid isomers. The present invention also relates to compositions containing such oligomers and co-oligomers and methods of use thereof.
In an effort to improve nutrition, the diets of ruminant animals have been supplemented with proteins and naturally occurring α-amino acids. Unfortunately, these proteins and α-amino acids can be subjected to extensive degradation in the rumen by ruminal microorganisms, thereby rendering the protein or amino acid unavailable to the animal for absorption. This is not a very efficient utilization of the feed, which is especially problematic in animals having increased nutritional requirements such as lactating dairy cows and fast growing animals such as beef cattle.
One approach to solving this problem has been to modify or protect the dietary protein or amino acid by a variety of chemical and physical methods so that it escapes degradation in the rumen. For example, heating soybean meal has shown some promise in producing protected proteins. However, the results were highly variable. Underheating the protein resulted in no protection while overheating the protein resulted in the degradation of important essential amino acids. See, for example, Plegge, S. D., Berger, L. L. and Fahey Jr. G. C. 1982. Effect of Roasting on Utilization of Soybean Meal by Ruminants. J. Anim. Sci. 55:395 and Faldet, M. A., Son, Y. S. and Satter, L. D. 1992. Chemical, in vitro and in vivo evaluation of soybean heat-treated by various processing methods. J. Dairy Sci. 75:789. Similarly, physical coating of proteins with materials such as fats and calcium soaps of fats has been met with mixed success.
Therefore, there is a need to somehow protect the protein from degradation in the rumen in order to make it available to the animal in the intestine where it can be properly absorbed. This would allow the animal to get increased nutritional benefit from the feed. Increasing the nutritional benefit of the feed can reduce the amount of feed required by the animals.
Dietary supplements such as proteins, naturally occurring α-amino acids, vitamins, minerals, and other nutrients are also used in aquaculture, (i.e., the cultivation of aquatic animals such as fish and crustaceans). Many of such supplements are difficult to provide, however, due to being soluble in water which causes the supplements to dissolve before they can be ingested. Dietary supplements for use in aquaculture therefore are preferably in an insoluble form in order to be ingested.
The role played by short chain peptides and their derivatives in the areas of nutrition science, flavor chemistry, and pharmacology has primed the advances in peptide chemistry. The inherent advantages of enzymatic peptide synthesis has led to its evolution as an alternative to chemical coupling methods (Fruton, J. S., 1992, Adv. Enzymology, 53, 239-306). The thiol-protease papain is reported to be the most efficient catalyst for aqueous phase synthesis of homooligomers of hydrophobic amino acids like leucine, methionine, phenylalanine, and tyrosine (A. Ferjancic, A. Puigserver and H.Gaertner, Biotech. Lett, 13(3) (1991) 161-166). The equilibria of such reactions is tilted in favor of synthesis by the precipitation of hydrophobic oligomers. However, the difficulty involved in the analysis of higher order, water insoluble oligomers, presents a unique challenge to biochromatography.